Leptin for Abnormal Lipid Kinetics in HIV Lipodystrophy Syndrome

NCT01511016 | Completed Results

• 1 other identifier: H-13372
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

"HIV lipodystrophy syndrome" (HLS) is characterized by loss of fat in the arms and legs, with increase in fat in the abdomen, and abnormal blood lipid levels. Persons with HLS have high risk for cardiovascular disease and diabetes mellitus and the metabolic syndrome. The investigators have previously shown that the abnormal lipid levels and lipodystrophy in HLS are associated with defective regulation of lipid metabolic rates, specifically, accelerated lipolysis (breakdown of stored fats), and decreased fat oxidation (utilization of fats for energy). Patients with HLS also have low levels of the hormone leptin. The investigators hypothesize that treatment of these patients with leptin will improve fat oxidation and may slow the rate of lipolysis. Hence, the investigators propose to study the effect of leptin therapy on lipid metabolic rates and lipid and glucose levels in adults with HLS. The investigators will use state of the art stable isotope tracer techniques and gas chromatography mass spectrometry (GCMS) to measure lipolysis, fat oxidation, and fat re-esterification in adipose tissues and liver.

Conditions

HIV Lipodystrophy

Keywords

lipid kinetics; fat oxidation

Outcome Measures

Primary Outcomes (2)

• Rate of Total Lipolysis

  Rate of total lipolysis was measured in plasma samples by mass spectrometry following stable isotope infusions of labeled glycerol and palmitate

  4 months after treatment

• Rate of Net Lipolysis

  Rate of net lipolysis was measured in plasma samples by mass spectrometry following stable isotope infusions of labeled glycerol and palmitate

  4 months after treatment

Secondary Outcomes (4)

• Rates of Fatty Acid Oxidation

  4 months after treatment

• Fasting Plasma Non-HDL-C

  4 months after treatment.

• Glucose Levels After Glucose Challenge

  4 months after treatment.

• Insulin Levels After Oral Glucose Challenge.

  4 months after treatment.

Study Arms (2)

human recombinant leptin (metreleptin)

EXPERIMENTAL

Each subject received 0.02 mg leptin / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg leptin / kg for two more months.

Drug: Human recombinant leptin ("metreleptin")

Placebo injection

PLACEBO COMPARATOR

Each subject received placebo at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by a dose of 0.04 mg / kg for two more months.

Drug: Placebo

Interventions

Human recombinant leptin ("metreleptin") DRUG

Metreleptin was administered at a dose of 0.02 mg / kg body weight for two months, followed by a dose of 0.04 mg / kg for two more months.

Also known as: metreleptin

human recombinant leptin (metreleptin)

Placebo DRUG

Placebo was administered at a dose of 0.02 mg / kg body weight daily by subcutaneous injection for two months, followed by 0.04 mg / kg for two more months.

Placebo injection

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• predominantly lipoatrophic or mixed phenotype of HIV-lipodystrophy (based on self-observation and evaluation by a study physician utilizing a visual scale;
• AM fasting leptin \< 4.0 ng/ml
• hypertriglyceridemia (fasting serum TG 250-1000 mg /dl).
• normal biochemistry (except altered lipid and glucose profile). Patients with the American Diabetes Association diagnostic criteria for diabetes were included provided the HbA1c level was \<7.5% and they received no anti-diabetic medications for at least 3 months.
• well-controlled HIV infection status evidenced by viral RNA titers \<400 copies/ml, on stable HAART.

You may not qualify if:

• acute or chronic illnesses.

Sponsors & Collaborators

• Baylor College of Medicine: lead

Study Sites (1)

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Sekhar RV, Jahoor F, Iyer D, Guthikonda A, Paranilam J, Elhaj F, Coraza I, Balasubramanyam A. Leptin replacement therapy does not improve the abnormal lipid kinetics of hypoleptinemic patients with HIV-associated lipodystrophy syndrome. Metabolism. 2012 Oct;61(10):1395-403. doi: 10.1016/j.metabol.2012.03.013. Epub 2012 Apr 28.

  PMID: 22542724 RESULT

MeSH Terms

Interventions

metreleptin

Limitations and Caveats

1. Relatively small sample size. 2. Early drop-out of 3 subjects (2 in placebo arm, 2 in metreleptin arm). 3. Possible confounders in phenotypic hetereogeneity of HIV lipodystrophy, and differences in antiretroviral drugs.

Results Point of Contact

• Title: Leanne Scott, PhD, Director of Sponsored Programs
• Organization: Baylor College of Medicine

lbscott@bcm.edu

713-798-6978

Study Officials

• Ashok Balasubramanyam, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: January 11, 2012
• First Posted: January 18, 2012
• Study Start: February 1, 2003
• Primary Completion: June 1, 2011
• Study Completion: October 1, 2011
• Last Updated: January 27, 2016
• Results First Posted: January 27, 2016

Record last verified: 2015-12

Locations

US (1)